The cardiovascular toxicity of the
• older generation of antidepressant drugs
such as tricyclic antidepressants is well
documented. These drugs inhibit cardiac
• and vascular ion channels causing life
threatening hypotension and arrhythmias.
Selective serotonin reuptake inhibitors
(SSRI) were introduced during the last
decade and their use is becoming
increasingly popular. Although these new
compounds are not more effective in
treating psychiatric disorders than the old
generation, they have fewer and more
benign cardi vascular, anticholinergic and
antihistaminic side effects. Recently, a
number of case reports have demonstrated
that the use of SSRIs is also associated with
the incidence of cases of arrhythmia and
orthostatic hypotension in some patients.
However, the data available concerning the
possible alteration by SSRIs of the vascular
4 neuroeffector system are not conclusive.
The present study was designed to test the
effect of one of the most popular SSRIs,
sertraline on the mean arterial pressure
(MAP) and heart rate (HR) of chronically
catheterized conscious rats. This rat
model was chosen to avoid the musking
effect of anaesthesia on central and
peripheral drug actions. The involvement of
the al receptors, the endothelium derived releasing factor/nitric oxide (EDRF/NO)
and prostaglandins in such effect was also
investigated. The dependence of sertraline
action on calcium or potassium entry
through their specific channels was also
explored. Sertraline bolus injection in 4
successive doses (10, 30, 100 and 300
μg/kg) did not induce any significant change
in basal MAP or HR. However, the same
doses induced dose dependent reduction of
MAP elevated and maintained by
angiotensin H (ATM or phenylephrine (PE)
infusion and the nitric oxide synthase
inhibitor L-nitro-arginine methyl ester (LNAME)
injection. Infusion of sertraline
(100 μg/kg/min) for 10 min neither
abolished the pressor effect of ATII (I, 3, 10
and 30 ng/kg) or PE (10, 30, 100 and 300
ng/kg) nor shifted their DRCs to the right.
The presence of indomethacin (1mg/kg)
attenuated and the presence of verapamil
(1mg/kg) potentiated the vasorelaxant
effect of sertraline. In contrast,
glibenclamide (1w/kg) injection neither
changed L-NAME elevated MAP nor
affected sertraline hypotensive response.
Thus, sertraline is not hypotensive or
arrhytlunogenic in basal states but inducrd a
vasorelaxant effect when MAP is elevated.
The vasorelaxant effect of sertraline may
involve Cr entry and prostaglandins
release but cc] receptor, K+ and NO
independent.